Effects of Hydroxychloroquine on Proteinuria in IgA Nephropathy: A Randomized Controlled Trial

Despite optimization of renin-angiotensin-aldosterone system (RAAS) inhibition, patients with immunoglobulin A nephropathy (IgAN) and persistent proteinuria remain at risk for kidney failure. We evaluated the efficacy and safety of hydroxychloroquine (HCQ), an immunomodulator, when added to the treatment regimen of patients with IgAN. Double-blind, randomized, placebo-controlled, phase 2 clinical trial. Participants had IgAN (proteinuria with protein excretion of 0.75-3.5g/d and estimated glomerular filtration rate>30mL/min/1.73m2) and were receiving optimized RAAS inhibitor therapy. Patients were randomly assigned 1:1 to receive daily oral HCQ or a placebo for 6 months. The primary outcome was percentage change in proteinuria between baseline and 6 months. 60 participants (mean estimated glomerular filtration rate, 53.8mL/min/1.73m2; median urine protein excretion, 1.7g/d) were recruited and randomly assigned to receive HCQ (n=30) or placebo (n=30). Percentage change in proteinuria at 6 months was significantly different between the HCQ group and the placebo group (−48.4% [IQR, −64.2%, −30.5%] vs 10.0% [IQR, −38.7%, 30.6%]; P